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Hereditary intrinsic platelet disorders are rare and produce lifelong bleeding tendencies. Diagnosis is confirmed by platelet aggregation tests. Platelet transfusion is necessary to control serious bleeding.
Normal hemostasis requires platelet adhesion and activation.
Adhesion (ie, of platelets to exposed vascular subendothelium) requires von Willebrand's factor (VWF) and the platelet glycoprotein Ib-IX complex.
Activation promotes platelet aggregation and fibrinogen binding and requires the platelet glycoprotein IIb-IIIa complex. Activation involves release of adenosine diphosphate (ADP) from platelet storage granules and conversion of arachidonic acid to thromboxane A2 via a cyclooxygenase-mediated reaction.
Hereditary intrinsic platelet disorders can involve defects in any of these substrates and steps. These disorders are suspected in patients with lifelong bleeding disorders who have normal platelet counts and coagulation study results. Diagnosis usually is based on platelet aggregation tests; however, platelet aggregation tests are not quantitative, and interpretation of results is often inconclusive (see Table 3: Thrombocytopenia and Platelet Dysfunction: Results of Aggregation Tests in Hereditary Disorders of Platelet Function ).
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Table 3
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| Results of Aggregation Tests in Hereditary Disorders of Platelet Function |
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Disorder
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Collagen, Epinephrine, and Low-Dose ADP
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High-Dose ADP
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Ristocetin
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Disorders of amplification of platelet activation
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Impaired
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Normal
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Normal
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Thrombasthenia
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Absent
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Absent
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Normal or impaired
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Bernard-Soulier syndrome
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Normal
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Normal
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Impaired
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ADP =
adenosine diphosphate.
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Disorders of adhesion:
Bernard-Soulier syndrome is a rare autosomal recessive disorder. It impairs platelet adhesion via a defect in the glycoprotein Ib-IX complex. Bleeding may be severe. Platelets are unusually large. They do not aggregate with ristocetin but aggregate normally with ADP, collagen, and epinephrine.
Large platelets associated with functional abnormalities also occur in the May-Hegglin anomaly, a thrombocytopenic disorder with abnormal WBCs, and in the Chédiak-Higashi syndrome (see Immunodeficiency Disorders: Chédiak-Higashi Syndrome).
Platelet transfusion is necessary to control serious bleeding.
Disorders of activation:
Disorders of amplification of platelet activation are the most common hereditary intrinsic platelet disorders and produce mild bleeding. They may result from decreased ADP in the platelet granules (storage pool deficiency), from an inability to generate thromboxane A2 from arachidonic acid, or from an inability of platelets to aggregate in response to thromboxane A2. Platelet aggregation tests reveal impaired aggregation after exposure to collagen, epinephrine, and low levels of ADP and normal aggregation after exposure to high levels of ADP. The same pattern can result from use of NSAIDs or aspirin, the effect of which can persist for several days. Therefore, platelet aggregation tests should not be done in patients who have recently taken these drugs.
Thrombasthenia (Glanzmann disease) is a rare autosomal recessive disorder causing a defect in the platelet glycoprotein IIb-IIIa complex; platelets cannot aggregate. Patients may experience severe mucosal bleeding (eg, nosebleeds that stop only after nasal packing and transfusions of platelet concentrates). The diagnosis is suggested by a finding of single platelets without aggregates on a peripheral blood smear obtained from a finger stick. It is confirmed by the finding that platelets fail to aggregate with epinephrine, collagen, or even high levels of ADP but do aggregate transiently with ristocetin. Platelet transfusion is necessary to control serious bleeding.
Last full review/revision May 2009 by James N. George, MD
Content last modified May 2009
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